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Report: Women have rare egg-producing stem cells

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Published : Feb. 27, 2012 - 09:56

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For 60 years, doctors have believed women were born with all the eggs they’ll ever have. Now Harvard scientists are challenging that dogma, saying they’ve discovered the ovaries of young women harbor very rare stem cells capable of producing new eggs.

If Sunday’s report is confirmed, harnessing those stem cells might one day lead to better treatments for women left infertile because of disease _ or simply because they’re getting older.

“Our current views of ovarian aging are incomplete. There’s much more to the story than simply the trickling away of a fixed pool of eggs,” said lead researcher Jonathan Tilly of Harvard’s Massachusetts General Hospital, who has long hunted these cells in a series of controversial studies.

Tilly’s previous work drew fierce skepticism, and independent experts urged caution about the latest findings. 

A key next step is to see whether other laboratories can verify the work. If so, then it would take years of additional research to learn how to use the cells, said Teresa Woodruff, fertility preservation chief at Northwestern University’s Feinberg School of Medicine.

Still, even a leading critic said such research may help dispel some of the enduring mystery surrounding how human eggs are born and mature.

“This is going to spark renewed interest, and more than anything else it’s giving us some new directions to work in,” said David Albertini, director of the University of Kansas’ Center for Reproductive Sciences. While he has plenty of questions about the latest work, “I’m less skeptical,” he said.

Scientists have long taught that all female mammals are born with a finite supply of egg cells, called ooctyes, that runs out in middle age. Tilly, Mass General’s reproductive biology director, first challenged that notion in 2004, reporting that the ovaries of adult mice harbor some egg-producing stem cells. Recently, Tilly noted, a lab in China and another in the U.S. also have reported finding those rare cells in mice.

But do they exist in women? Enter the new work, reported Sunday in the journal Nature Medicine.

First Tilly had to find healthy human ovaries to study. He collaborated with scientists at Japan’s Saitama Medical University, who were freezing ovaries donated for research by healthy 20-somethings who underwent a sex-change operation.

Tilly also had to address a criticism: How to tell if he was finding true stem cells or just very immature eggs. His team latched onto a protein believed to sit on the surface of only those purported stem cells and fished them out. To track what happened next, the researchers inserted a gene that makes some jellyfish glow green into those cells. If the cells made eggs, those would glow, too.

“Bang, it worked _ cells popped right out” of the human tissue, Tilly said.

Researchers watched through a microscope as new eggs grew in a lab dish. Then came the pivotal experiment: They injected the stem cells into pieces of human ovary. They transplanted the human tissue under the skin of mice, to provide it a nourishing blood supply. Within two weeks, they reported telltale green-tinged egg cells forming.

That’s still a long way from showing they’ll mature into usable, quality eggs, Albertini said.

And more work is needed to tell exactly what these cells are, cautioned reproductive biologist Kyle Orwig of the University of Pittsburgh Medical Center, who has watched Tilly’s work with great interest.

But if they’re really competent stem cells, Orwig asked, then why would women undergo menopause? Indeed, something so rare wouldn’t contribute much to a woman’s natural reproductive capacity, added Northwestern’s Woodruff.

Tilly argues that using stem cells to grow eggs in lab dishes might one day help preserve cancer patients’ fertility. Today, Woodruff’s lab and others freeze pieces of girls’ ovaries before they undergo fertility-destroying chemotherapy or radiation. They’re studying how to coax the immature eggs inside to mature so they could be used for in vitro fertilization years later when the girls are grown. If that eventually works, Tilly says stem cells might offer a better egg supply.

Further down the road, he wonders if it also might be possible to recharge an aging woman’s ovaries.

The new research was funded largely by the National Institutes of Health. Tilly co-founded a company, OvaScience Inc., to try to develop the findings into fertility treatments. (AP)

 

<관련 한글 기사>


美연구진, 난소 인공 배양 성공


미국 연구팀이 인간의 난소에서 줄기세포를 재취, 난자로 분화시키는 데 성공함으로써 불임 치료 등에 획기적인 전기를 가져올 것으로 보인다.

여성은 출생시 평생 쓸 일정량의 난자를 가지고 태어나며 나이를 먹으면서 점점 고갈돼 폐경과 함께 완전 소진되는 것으로 알려져 있다. 

미국 매사추세츠 종합병원 생식생물학연구실장 조너선 틸리(Jonathan Tilly) 박 사는 성인여성의 난소에는 난자의 전구세포인 난모세포를 만드는 줄기세포가 존재하며 실제로 이 줄기세포를 난소조직에서 채취해 난모세포를 거쳐 난자로 성숙시키는 데 성공했다고 밝힌 것으로 AP, AFP통신 등이 26일(현지시간) 보도했다.

그의 연구팀은 먼저 일본 사이타마(埼玉) 의대에서 성전환수술을 위해 난소를 제거한 건강한 20대 여성으로부터 난소조직을 기증받아 줄기세포를 채취, 이를 난모 세포로 배양했다.

난소조직에서 줄기세포를 골라내는 데는 중국 상하이 자오퉁(上海交通) 대학 연구팀이 개발한 방법을 사용했다. 즉 이 줄기세포만이 가지는 표지단백질(Ddx4)을 찾 는 것이다.

연구팀은 난모세포에 해파리의 푸른빛을 내는 유전자를 주입한 뒤 인간의 난소 조직에 넣었다. 이어 이 난소조직을 쥐의 피부 밑에 심어 혈액이 공급되도록 했다.

그 결과 14일만에 성숙된 난자가 생성되었다. 이 난자들 중 일부는 푸른빛을 띠고 있었다. 이들이 형광유전자가 주입된 난모세포에서 나왔다는 증거다. 푸른빛이 없는 난자들은 원래 난소조직에 들어있던 난모세포가 난자로 성장했음을 보여주는 것이다. 

이 연구결과는 인간 난소조직에는 난모세포를 만드는 줄기세포가 존재한다는 사실과 여를 난모세포를 거쳐 성숙한 난자로 만들 수 있음을 확인한 것이라고 틸리 박사는 말했다.  

릴리 박사는 이는 또 인간의 난자를 무한히 만들어 낼 수 있음을 보여주는 것이라면서 앞으로 항암치료를 받는 여성환자나 일반여성의 난소로부터 줄기세포를 채취 해 냉동보관해 두었다가 나중 아기를 갖고 싶을 때 찾아 쓸 수 있는 난소줄기세포은행을 만들 계획이라고 밝혔다.

난자자체를 내동보관했다가 쓸 수도 있지만 이는 해동 과정에서 손상될 위험이 있다. 그러나 난소줄기세포는 이러한 위험이 없다고 릴리 박사는 말했다.  

이 연구결과는 영국의 의학전문지 '네이처 메디신(Nature Medicine)' 최신호에 발표되었다. (연합뉴스)